CA2538174A1 - Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini - Google Patents
Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini Download PDFInfo
- Publication number
- CA2538174A1 CA2538174A1 CA002538174A CA2538174A CA2538174A1 CA 2538174 A1 CA2538174 A1 CA 2538174A1 CA 002538174 A CA002538174 A CA 002538174A CA 2538174 A CA2538174 A CA 2538174A CA 2538174 A1 CA2538174 A1 CA 2538174A1
- Authority
- CA
- Canada
- Prior art keywords
- oligomeric compound
- independently
- oligomeric compounds
- rna
- target
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 307
- 235000000346 sugar Nutrition 0.000 title claims description 79
- 125000002619 bicyclic group Chemical group 0.000 title claims description 28
- 239000002777 nucleoside Substances 0.000 claims abstract description 123
- 150000003833 nucleoside derivatives Chemical class 0.000 claims abstract description 64
- -1 -CH3 modified nucleoside, a 2 Chemical class 0.000 claims description 273
- 238000000034 method Methods 0.000 claims description 69
- 125000003835 nucleoside group Chemical group 0.000 claims description 65
- 230000014509 gene expression Effects 0.000 claims description 47
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 32
- 125000006239 protecting group Chemical group 0.000 claims description 32
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 150000004713 phosphodiesters Chemical class 0.000 claims description 27
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 26
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 25
- 229920001577 copolymer Polymers 0.000 claims description 23
- 229940035893 uracil Drugs 0.000 claims description 23
- 125000005647 linker group Chemical group 0.000 claims description 22
- 239000007787 solid Substances 0.000 claims description 22
- 229930024421 Adenine Natural products 0.000 claims description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 18
- 229960000643 adenine Drugs 0.000 claims description 18
- 229940104302 cytosine Drugs 0.000 claims description 18
- 229920000642 polymer Polymers 0.000 claims description 18
- 241001465754 Metazoa Species 0.000 claims description 17
- 239000005289 controlled pore glass Substances 0.000 claims description 17
- 238000006467 substitution reaction Methods 0.000 claims description 17
- PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 claims description 16
- 239000004793 Polystyrene Substances 0.000 claims description 16
- 229940113082 thymine Drugs 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 229920002223 polystyrene Polymers 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 14
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 claims description 14
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 claims description 14
- HCGHYQLFMPXSDU-UHFFFAOYSA-N 7-methyladenine Chemical compound C1=NC(N)=C2N(C)C=NC2=N1 HCGHYQLFMPXSDU-UHFFFAOYSA-N 0.000 claims description 14
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 14
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 14
- 150000001408 amides Chemical class 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 claims description 14
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 claims description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 10
- 208000035139 partial with pericentral spikes epilepsy Diseases 0.000 claims description 10
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- 239000000377 silicon dioxide Substances 0.000 claims description 8
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- UHUHBFMZVCOEOV-UHFFFAOYSA-N 1h-imidazo[4,5-c]pyridin-4-amine Chemical compound NC1=NC=CC2=C1N=CN2 UHUHBFMZVCOEOV-UHFFFAOYSA-N 0.000 claims description 7
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 claims description 7
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 claims description 7
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 claims description 7
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 claims description 7
- KXBCLNRMQPRVTP-UHFFFAOYSA-N 6-amino-1,5-dihydroimidazo[4,5-c]pyridin-4-one Chemical compound O=C1NC(N)=CC2=C1N=CN2 KXBCLNRMQPRVTP-UHFFFAOYSA-N 0.000 claims description 7
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 claims description 7
- QNNARSZPGNJZIX-UHFFFAOYSA-N 6-amino-5-prop-1-ynyl-1h-pyrimidin-2-one Chemical compound CC#CC1=CNC(=O)N=C1N QNNARSZPGNJZIX-UHFFFAOYSA-N 0.000 claims description 7
- LOSIULRWFAEMFL-UHFFFAOYSA-N 7-deazaguanine Chemical compound O=C1NC(N)=NC2=C1CC=N2 LOSIULRWFAEMFL-UHFFFAOYSA-N 0.000 claims description 7
- HRYKDUPGBWLLHO-UHFFFAOYSA-N 8-azaadenine Chemical compound NC1=NC=NC2=NNN=C12 HRYKDUPGBWLLHO-UHFFFAOYSA-N 0.000 claims description 7
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 claims description 7
- 229960005508 8-azaguanine Drugs 0.000 claims description 7
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 claims description 7
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 claims description 7
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000005524 levulinyl group Chemical group 0.000 claims description 7
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 7
- AYGYHGXUJBFUJU-UHFFFAOYSA-N n-[2-(prop-2-enoylamino)ethyl]prop-2-enamide Chemical compound C=CC(=O)NCCNC(=O)C=C AYGYHGXUJBFUJU-UHFFFAOYSA-N 0.000 claims description 7
- 125000003431 oxalo group Chemical group 0.000 claims description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 7
- FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical compound OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 7
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 7
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 229940075420 xanthine Drugs 0.000 claims description 7
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 6
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 6
- 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 6
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- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 6
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 6
- 125000005600 alkyl phosphonate group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
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- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 4
- CWGKROHVCQJSPJ-UHFFFAOYSA-N oxathiasilirane Chemical compound O1[SiH2]S1 CWGKROHVCQJSPJ-UHFFFAOYSA-N 0.000 claims description 4
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims description 4
- NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 claims description 3
- URBXHNSZZLMBOT-UHFFFAOYSA-N n-[9-(4-fluoro-3,5,6-trihydroxyoxan-2-yl)purin-6-yl]benzamide Chemical class OC1C(F)C(O)C(O)OC1N1C2=NC=NC(NC(=O)C=3C=CC=CC=3)=C2N=C1 URBXHNSZZLMBOT-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US60/501,719 | 2003-09-09 | ||
| US56803904P | 2004-05-03 | 2004-05-03 | |
| US60/568,039 | 2004-05-03 | ||
| US56848904P | 2004-05-06 | 2004-05-06 | |
| US60/568,489 | 2004-05-06 | ||
| US10/872,106 US20050053981A1 (en) | 2003-09-09 | 2004-06-18 | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
| US10/872,106 | 2004-06-18 | ||
| PCT/US2004/029650 WO2005023825A2 (en) | 2003-09-09 | 2004-09-09 | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
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| CA2538174A1 true CA2538174A1 (en) | 2005-03-17 |
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| CA002538174A Abandoned CA2538174A1 (en) | 2003-09-09 | 2004-09-09 | Gapped oligomeric compounds having linked bicyclic sugar moieties at the termini |
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| CA (1) | CA2538174A1 (enrdf_load_stackoverflow) |
| WO (1) | WO2005023825A2 (enrdf_load_stackoverflow) |
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| US20050191653A1 (en) * | 2003-11-03 | 2005-09-01 | Freier Susan M. | Modulation of SGLT2 expression |
| WO2006034348A2 (en) * | 2004-09-17 | 2006-03-30 | Isis Pharmaceuticals, Inc. | Enhanced antisense oligonucleotides |
| JP2009508528A (ja) * | 2005-09-19 | 2009-03-05 | ジヨンソン・アンド・ジヨンソン・フアーマシユーチカル・リサーチ・アンド・デベロツプメント・エルエルシー | グルカゴン受容体発現の調節 |
| US20070066557A1 (en) * | 2005-09-19 | 2007-03-22 | Monia Brett P | Modulation of glucocorticoid receptor expression |
| US8143230B2 (en) * | 2006-05-05 | 2012-03-27 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of PCSK9 |
| EP2410054B2 (en) † | 2006-10-18 | 2019-12-11 | Ionis Pharmaceuticals, Inc. | Antisense compounds |
| WO2009002150A1 (en) * | 2007-06-22 | 2008-12-31 | Keygene N.V. | Targeted nucleotide exchange with improved modified oligonucleotides |
| DK2195428T3 (en) * | 2007-09-19 | 2014-03-03 | Applied Biosystems Llc | SIRNA SEQUENCE-INDEPENDENT MODIFICATION FORMS TO REDUCE TARGET-FAILING PHENOTYPIC EFFECTS OF RNAI, AND STABILIZED FORMS THEREOF |
| US9290534B2 (en) * | 2008-04-04 | 2016-03-22 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds having at least one neutrally linked terminal bicyclic nucleoside |
| WO2010000656A1 (en) * | 2008-07-03 | 2010-01-07 | Santaris Pharma A/S | Rna antagonist compounds for the inhibition of expression of mitochondrial glycerol-3-phosphate acyltransferase 1 (mtgpat1) |
| AU2009323766B2 (en) | 2008-12-02 | 2016-10-06 | Wave Life Sciences Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| IN2012DN00720A (enrdf_load_stackoverflow) | 2009-07-06 | 2015-06-19 | Ontorii Inc | |
| US8563528B2 (en) | 2009-07-21 | 2013-10-22 | Santaris Pharma A/S | Antisense oligomers targeting PCSK9 |
| US8255305B2 (en) * | 2009-09-15 | 2012-08-28 | Chicago Mercantile Exchange Inc. | Ratio spreads for contracts of different sizes in implied market trading |
| DK2620428T3 (da) | 2010-09-24 | 2019-07-01 | Wave Life Sciences Ltd | Asymmetrisk hjælpegruppe |
| EP3467109A1 (en) | 2011-02-08 | 2019-04-10 | Ionis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| US9605019B2 (en) | 2011-07-19 | 2017-03-28 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| EP3922722B1 (en) | 2011-08-11 | 2023-06-28 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| JP6129844B2 (ja) | 2011-09-14 | 2017-05-17 | ラナ セラピューティクス インコーポレイテッド | 多量体オリゴヌクレオチド化合物 |
| RU2598709C2 (ru) | 2011-09-20 | 2016-09-27 | Айсис Фармасьютикалс, Инк. | Антисмысловая регуляция экспрессии gcgr |
| EP2771463A4 (en) | 2011-10-25 | 2015-09-09 | Isis Pharmaceuticals Inc | ANTISENSE MODULATION OF GCCR EXPRESSION |
| WO2013159108A2 (en) | 2012-04-20 | 2013-10-24 | Isis Pharmaceuticals, Inc. | Oligomeric compounds comprising bicyclic nucleotides and uses thereof |
| WO2014012081A2 (en) | 2012-07-13 | 2014-01-16 | Ontorii, Inc. | Chiral control |
| CA2879023C (en) | 2012-07-13 | 2017-03-28 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| RU2677639C2 (ru) | 2012-07-13 | 2019-01-18 | Шин Ниппон Биомедикал Лэбораториз, Лтд. | Хиральный адъювант нуклеиновой кислоты |
| DK2895200T3 (da) | 2012-09-14 | 2020-02-10 | Translate Bio Ma Inc | Multimeriske oligonukleotidforbindelser |
| EP2906699A4 (en) | 2012-10-11 | 2016-06-08 | Ionis Pharmaceuticals Inc | OLIGOMER COMPOUNDS WITH BICYCLIC NUCLEOSIDES AND USES THEREOF |
| US10260089B2 (en) | 2012-10-29 | 2019-04-16 | The Research Foundation Of The State University Of New York | Compositions and methods for recognition of RNA using triple helical peptide nucleic acids |
| WO2014207232A1 (en) | 2013-06-27 | 2014-12-31 | Santaris Pharma A/S | Antisense oligomers and conjugates targeting pcsk9 |
| JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| EP3095459A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
| DK3094728T3 (da) | 2014-01-16 | 2022-05-16 | Wave Life Sciences Ltd | Kiralt design |
| GB201410693D0 (en) | 2014-06-16 | 2014-07-30 | Univ Southampton | Splicing modulation |
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-
2004
- 2004-06-18 US US10/872,106 patent/US20050053981A1/en not_active Abandoned
- 2004-09-08 US US10/935,958 patent/US8703728B2/en active Active
- 2004-09-09 CA CA002538174A patent/CA2538174A1/en not_active Abandoned
- 2004-09-09 JP JP2006526330A patent/JP2007505138A/ja active Pending
- 2004-09-09 AU AU2004270741A patent/AU2004270741B2/en not_active Ceased
- 2004-09-09 EP EP04788694A patent/EP1670810A4/en not_active Withdrawn
- 2004-09-09 WO PCT/US2004/029650 patent/WO2005023825A2/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| EP1670810A2 (en) | 2006-06-21 |
| JP2007505138A (ja) | 2007-03-08 |
| AU2004270741A1 (en) | 2005-03-17 |
| WO2005023825A2 (en) | 2005-03-17 |
| AU2004270741B2 (en) | 2011-02-24 |
| WO2005023825A3 (en) | 2005-12-22 |
| US20050053981A1 (en) | 2005-03-10 |
| US8703728B2 (en) | 2014-04-22 |
| US20050059066A1 (en) | 2005-03-17 |
| EP1670810A4 (en) | 2010-05-26 |
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